Long-term tolerability of once-monthly injectable paliperidone palmitate in subjects with recently diagnosed schizophrenia

Abstract

Background: A post hoc analysis from a multiphase trial with open-label transition and maintenance phases, a double-blind relapse prevention phase, and an optional open-label extension examined the long-term tolerability with continuous once-monthly injectable paliperidone palmitate 39, 78, 117, or 156 mg (25, 50, 75, or 100 mg equivalents [mg eq] of paliperidone) in subjects with recently diagnosed (≤5 years; n = 216) versus chronic illness (>5 years; n = 429) schizophrenia.

Methods: Adverse events reported at a ≥2% margin between subgroups were identified. Relative risks (in the recently diagnosed compared with the chronically ill) and 95% confidence intervals (CI) were determined, and CI not including 1 were considered potentially significant.

Results: In both subgroups, the mean monthly dose was 109 mg (69.9 mg eq). Continuous mean exposures were 333.9 ± 271.9 and 308.7 ± 278.3 days in the recently diagnosed and chronic illness subgroups, respectively. Using the criteria outlined in the methods, nasopharyngitis was a potentially significant event reported in more chronically ill than recently diagnosed subjects at months 6, 9, 12, and endpoint (7.2% versus 2.8%; relative risk 0.384; 95% CI 0.163-0.907). Influenza (2.8% versus 0.7%; relative risk 3.9; 95% CI 1.003-15.730) and amenorrhea (3.2% versus 0.9%; relative risk 3.476; 95% CI 1.029-11.744) at endpoint were potentially significant events in more recently diagnosed than chronically ill subjects. Mean weight changes, sedation/somnolence, any extrapyramidal symptom-related or glucose-related events were generally similar between the groups. The mean prolactin level increased in both sexes in both subgroups (changes from baseline of +41.8 ng/mL and +26.5 ng/mL in recently diagnosed and chronic illness females and +12.3 ng/mL and +15.1 ng/mL in recently diagnosed and chronic illness males, respectively), and were higher in females with recently diagnosed illness than in females who were chronically ill (P = 0.0002 at endpoint). Prolactin-related events were reported by 7.9% of recently diagnosed subjects with schizophrenia and 3.5% of those who were chronically ill.

Conclusion: The long-term tolerability of paliperidone palmitate was generally similar in recently diagnosed schizophrenia subjects and those with more chronic illness, with the exception of some prolactin-related measures.

Keywords: early illness; long-acting antipsychotic; paliperidone palmitate; recently diagnosed; schizophrenia.

Figure 1

Study design and subject disposition in recently diagnosed and chronically ill subgroups treated continuously with paliperidone palmitate. Note: +74 subjects who were in the maintenance phase at the time of its termination and were considered to have completed this phase were eligible to enroll in the open-label extension without entering the double-blind phase. Of the 58 that enrolled, 26 were recently diagnosed and 32 were in the chronic illness subgroup.

Figure 2

Percentage, relative risk (recently diagnosed versus chronic illness), and 95% confidence intervals of adverse events reported by a margin of ≥2% in recently diagnosed or chronically ill subgroups.

Figure 3

Percentage of Subjects with Any EPS-Related Event* from First Injection to Specified Timepoint, in Recently Diagnosed and Chronic Illness Subjects. Note: *Any EPS-related events include tremor, dystonia, hyperkinesia, parkinsonims, extrapyramidal disorder and dyskinesia, and each of their preferred terms.